Thrombin generation in different cohorts: Evaluation of the haemostatic potential

Chaireti, Roza

doi:10.3384/diss.diva-100218

Cited by 3 publications

(4 citation statements)

References 172 publications

(230 reference statements)

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“…Our study also investigated TG in PCOS, a test that assesses the formation of thrombin following activation of the coagulation cascade by tissue factor. TG is a global hemostatic assay that looks at both the procoagulation effects of the coagulation cascade, but also at inhibitory substances that prevent the generation of thrombin, mainly tissue factor pathway inhibitor, antithrombin (AT) and protein C. 42 TG is very sensitive to variations of prothrombin and AT, as well as to the activity of activated protein C system. 42 Our study showed no significant difference between PCOS and controls with regard to TG (►Table 2).…”

Section: Discussionmentioning

confidence: 99%

“…TG is a global hemostatic assay that looks at both the procoagulation effects of the coagulation cascade, but also at inhibitory substances that prevent the generation of thrombin, mainly tissue factor pathway inhibitor, antithrombin (AT) and protein C. 42 TG is very sensitive to variations of prothrombin and AT, as well as to the activity of activated protein C system. 42 Our study showed no significant difference between PCOS and controls with regard to TG (►Table 2). Although the PF1 & 2 and TG results do not suggest an overall prothrombotic state, the TG assay does not take into account the effects of fibrinolysis, the markers of which mainly act upon fibrinogen and fibrin, activated downstream from thrombin in the coagulation cascade.…”

Section: Discussionmentioning

confidence: 99%

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Comprehensive Assessment of the Hemostatic System in Polycystic Ovarian Syndrome

Burchall

Piva

Linden

et al. 2015

Semin Thromb Hemost

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Polycystic ovarian syndrome (PCOS) affects 12 to 19% of women and has reproductive and metabolic features (endothelial dysfunction, increased diabetes, and cardiovascular risk factors). It also appears to have altered coagulation and fibrinolysis with a prothrombotic state with epidemiological evidence of increased venous thromboembolism. We aimed to comprehensively assess hemostasis in women with PCOS versus control women. In an established case-control cohort of lean, overweight, and obese women with (n = 107) and without PCOS (n = 67), with existing measures of plasminogen activator inhibitor 1 (PAI-1), asymmetric dimethylarginine (ADMA), hormonal, and metabolic markers, we also assessed prothrombin fragments 1 and 2 (PF1 & 2), plasminogen, tissue plasminogen activator (tPA), and thrombin generation (TG). Higher levels of ADMA (0.70 vs. 0.39 µmol/L, p < 0.01), PAI-1 (4.80 vs. 3.66 U/mL, p < 0.01), and plasminogen (118.39 vs. 108.46%, p < 0.01) were seen in PCOS versus controls, and persisted after adjustment for age and body mass index (BMI). PF1 & 2 was marginally lower (180.0 vs. 236.0 pmol/L, p = 0.05), whereas tPA and TG were not different between groups, after adjustment for age and BMI. Significant relationships were observed between hormonal and metabolic factors with ADMA and PAI-1. We demonstrate impaired fibrinolysis in PCOS. In the context of abnormal endothelial function and known hormonal and metabolic abnormalities, this finding may underpin an increased risk of cardiovascular disease and venous thrombosis in PCOS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comprehensive Assessment of the Hemostatic System in Polycystic Ovarian Syndrome

Burchall

Piva

Linden

et al. 2015

Semin Thromb Hemost

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“…Finally, the analysis program calculated all parameters of the thrombogram, which are characterized by the following main parameters: The lag time is the clotting time, the moment at which TG begins. The peak height, that is, the maximum thrombin concentration, in nanomolar thrombin. The time to peak (ttpeak), that is, the time to reach the maximum thrombin concentration. The endogenous thrombin potential (ETP), Area Under the Curve (AUC), the total amount of thrombin generated, in nanomolar minute. The start tail, time at which the TG came to an end, in minutes. 16 …”

Section: Methodsmentioning

confidence: 99%

Evaluation of Thrombin Generation Assay in Patients With Hemophilia

Haghpanah

Bazrafshan

Silavizadeh

et al. 2014

Clin Appl Thromb Hemost

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We evaluated the correlation between thrombin generation (TG) parameters with bleeding symptoms and disease severity in patients with hemophilia. In this cross-sectional study, 59 patients with hemophilia without inhibitors and regardless of their severity were randomly selected from southern Iran and TG assays were conducted. Bleeding score (BS) was calculated by performing a clinical evaluation using Tosetto questionnaire. Only lag time showed a statistically significant correlation with BS (rs = .316,P= .016). All TG parameters except peak showed association with disease severity (P< .05). Endogenous thrombin potential showed a significant correlation with factor activity level (rs = .459,P< .001). Both lag time and start tail showed significant negative correlations with factor activity level (rs = -0.488,P< .001 andrs = - .289,P< .026, respectively). Although most of the TG parameters evaluated were not significantly correlated with the BS of patients with hemophilia, the majority of TG parameters were significantly associated with factor activity level and disease severity.

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“…10 In our study, PF1 and 2 levels significantly increased in the higher-dose OCP group but not in the low-dose group. We also investigated TG, a global haemostatic assay that looks at both the pro-coagulation effects of the coagulation cascade, but also at inhibitory substances that prevent the generation of thrombin, mainly tissue factor pathway inhibitor, anti-thrombin and protein C. 41 TG levels are also similar in women with PCOS compared with controls. 10 Here, TG was significantly increased after higher-and low-dose OCP in women with PCOS.…”

Section: Effects On Coagulation (Secondary Haemostasis)mentioning

confidence: 99%

Differential Effects on Haemostatic Markers by Metformin and the Contraceptive Pill: A Randomized Comparative Trial in PCOS

Burchall¹,

Piva²,

Ranasinha³

et al. 2017

Thromb Haemost

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Polycystic ovarian syndrome (PCOS) affects up to 18% of reproductive-aged women with increased risks of cardiovascular disease and venous thromboembolic disease, related to metabolic and hormonal features, obesity and an apparent hypofibrinolytic state, possibly exacerbated by current PCOS treatments. To investigate and compare haemostatic impacts of common pharmacological treatments and explore relationships with hormonal and metabolic variables in PCOS. This mechanistic sub-study using biobanked samples from a 6-month randomized comparative trial of pharmacological treatments assessed pro- and anti-thrombotic markers and overall haemostatic activity. Overweight women of mean age 33.9 ± 6.7 years and mean BMI (body mass index) of 36.5 ± 7.0 kg/m with PCOS ( = 60) were randomized to either metformin, higher-dose oral contraceptive pill (OCP) or low-dose OCP + spironolactone (OCP + S). Primary outcome measures included changes in plasminogen activator inhibitor 1 (PAI-1), asymmetric dimethylarginine (ADMA), prothrombin fragments 1 and 2 (PF1 and 2), plasminogen, tissue plasminogen activator (tPA), thrombin activatable fibrinolysis inhibitor (TAFI) and thrombin generation (TG). PAI-1 activity fell in all groups, ADMA fell in higher-dose OCP, PF1 and 2 increased with metformin and higher-dose OCP, TG rose and tPA fell in both OCP groups, plasminogen increased in all and TAFI increased after higher-dose OCP. Endothelial function (primary haemostasis) improved with higher dose with some improvement in low-dose OCP + S and metformin. Aberrant coagulation was noted in both OCP groups, but not with metformin. Fibrinolysis was reduced with higher-dose OCP. Our work suggests an additional dimension of treatment (haemostatic system effects) that favours metformin treatment over the OCP in PCOS.

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Thrombin generation in different cohorts: Evaluation of the haemostatic potential

Cited by 3 publications

References 172 publications

Comprehensive Assessment of the Hemostatic System in Polycystic Ovarian Syndrome

Comprehensive Assessment of the Hemostatic System in Polycystic Ovarian Syndrome

Evaluation of Thrombin Generation Assay in Patients With Hemophilia

Differential Effects on Haemostatic Markers by Metformin and the Contraceptive Pill: A Randomized Comparative Trial in PCOS

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